A brief history of transplant technologyAlthough there are some accounts of experimental transplantstaking place as early as second century BC, the time-line belowgives details of the first successful documented examples.

1905 First successful cornea transplant performed byEduard Zirm (In China the main source of organsfor transplant is from executed prisoners)

1954 First kidney transplant by Joseph Murray, USA

1966 First pancreatic transplant by Lillehei and Kelly,USA

1967 First successful heart transplant by ChristiaanBarnard, South Africa

1981 First heart-lung transplant by Bruce Reitz, USA

1986 First successful double-lung transplant by JoelCooper, Canada

1998 First live-donor partial pancreatic transplant byDavid Sutherland, USA

2005 First successful partial face transplant,Devauchelle and Dubernard, France

2006 First successful penis transplant by Hu Weilie,China

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Number 194www.curriculum-press.co.uk

Tissue and Organ TransplantsTransplants are a favourite synoptic topic; and ethical issues arebecoming more common on all of the A level specifications.

This Factsheet summarises:• The main types of transplant• The difficulties that have to be overcome to stop rejection• Ethical issues surrounding transplants• Typical exam questions you are likely to face

An organ transplant is the moving of a whole (or part of) an organfrom one person’s body to another. It is always done to help patientswhose organ has failed in some way or is diseased.

Over 2,300 transplant operations are performed annually in the UK(Fig1), but there are over 7,000 people on the waiting list to receivea new organ – this reflects a shortage of supply. This gives rise toa number of ethical considerations surrounding the circumstancesunder which someone should donate an organ for transplant.

Fig 1. Transplants UK

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

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transplantstransplant list

Types of organ transplantationKidney and heart are the most commonly performed transplantoperations. However, a whole host of other organs and tissuesfrom the body can be transplanted nowadays from the liver, pancreasand intestines to heart valves and bone marrow.

Most transplant operations involve transplantation from one humanto another with similar immune systems so that the tissues ‘match’.However, it is possible to transplant across different species(xenotranplantation). Some doctors believe this could be a meansof solving the supply problems we are currently facing. However, itraises a number of ethical, religious and safety issues which willhave to be resolved.

year

Table 1 Key terms

Term used Description

Allograft Transplant between geneticallydifferent members of the same species

Isograft Transplant between geneticallyidentical members of the same species(e.g. identical twins or even a clone)

Xenograft Transplantation from one species to(xenotransplantation) another (e.g. a pig to a human)

Domino transplant Transplanting 2 organs at a time. Forexample, if a patient needs new lungsit is easier to transplant the lungs andheart together. The recipients heart canthen be used for another patient.

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www.curriculum-press.co.uk194. Tissue and Organ Transplants

Transplant biologyThe main difficulty relates to the patient’s immune system. Because the donor organ doesn’t belong to the patient, the immune systemsees it as foreign/antigenic and launches an attack on the newly transplanted tissue. Lymphocytes release antibodies which attack theorgan and this leads to rejection.

The flow chart shows what happens when an antigen enters our body (Fig 2)

Antigen invadesbody for first time(antigen could, forexample be a proteinon the outside of abacterium)

Antigen binds to aB lymphocyte (B cell)

B cells mulitplyby mitosis

Some B cellsbecome plasmacells

Plasma cellssecrete antibodywhich destroysthe antigen

Some B cellsbecomememory cells

If antigen invadesagain, memory cellsinstantly recogniseit and start secretingantibody to destroythe antigen. Theresponse is so fastyou may not evenhave any symptoms

Fig 2

If this is not controlled, the patient often dies. Drugs which suppressor slow down the patient’s immune system were first discovered inthe late 1950’s. These so-called immunosuppressants (the mostfamous of which is called cyclosporine) revolutionisedtransplantation surgery because they stopped the organ beingrejected.

However, suppressing the patient’s immune system makes themmore likely to get other infections. The challenge is to develop adrug which stops rejection but doesn’t suppress the immune systemto the extent that the patient becomes vulnerable to infections.

Often in synoptic topics like this, you will be asked to apply basicprinciples to unfamiliar topics or to combine bits of knowledge ofdifferent areas of the specification– the secret is not to panic! Thefollowing question combines transplants with glucose regulation.

Typical Exam QuestionGene therapy is used to treat the genetic disorder, ADAdeficiency. Affected individuals are unable to produce theenzyme adenosine deaminase (ADA). Without this enzyme,T lymphocytes, a type of white blood cell, cannot provideimmunity to infection.

T lymphocytes are produced in bone marrow. A bone marrowtransplant from a genetically matched donor can provide apermanent cure for ADA deficiency.

(a) Suggest why bone marrow for a transplant is obtained from agenetically matched donor. (1 mark)

(b) Explain why treatment of ADA deficiency by gene therapymust be repeated at regular intervals, whereas a single bonemarrow transplant can provide a permanent cure. (2 marks)

Markscheme(a) to .prevent. rejection / immune response; 1(b) T lymphocytes have a limited life span / do not reproduce;

bone marrow provides continual supply of T lymphocytes; 2

Typical Exam QuestionMany diabetics inject insulin because their pancreas has stoppedproducing it. Attempts have been made to transplant pancreaticcells from human embryos into diabetics but these foreign cellsare often destroyed by the diabetic’s immune system.

The diagram shows a new type of transplant which has beentested in rats.

Glucose molecule

Antibodymolecule

Spongy materialholding pancreaticcells from a pig

Silicon boxwith smallpores inthe walls

(a) (i) Explain why this transplant is not destroyed by the ratbut can respond to changes in the rat’s blood glucoseconcentration. (2 marks)

(ii) Suggest why there might be controversy if this transplantwas used in humans. (1 mark)

(b) Explain how the cells in the transplant control the bloodglucose concentration of the rat. (3 marks)

Markscheme(a) (i) antibody too big to get through pores (and attack cells);

glucose small enough to (diffuse) enter / hormones canleave;protects from lymphocytes / no antigen on silicon box; 2 max

(ii) killing animals to use for human (transplant);religious objections;1 max

(b) rise/fall in rat blood sugar means more/less glucose enters(diffuses) into box;detected by animal pancreas cells that release insulin/glucagon;insulin (diffuses) into rat’s blood;insulin/glucagon makes rat’s cells take up/release moreglucose; 3 max

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www.curriculum-press.co.uk194. Tissue and Organ Transplants

SafetyAnother major problem with transplantation surgery is the risk oftransmitting a blood-borne disease. If the donor is HIV+ (the virusthat leads to AIDS) or carries hepatitis (a liver disease), then it islikely that this will be transmitted to, (or caught by), the patientreceiving the organ. All donors are screened in developed countrieslike the UK, but in the developing world efficient screening cannotbe guaranteed.

The supply of donor organsThe largest supply of donor organs comesfrom people who have died but whoseorgans are still functioning and healthy(for example following a car accident).Currently in the UK a donor must giveconsent for organs or tissues to be usedin this way by carrying a Donor Card (seewww.uktransplant.org.uk for further information). If a recentlydeceased person is suitable as a donor, but hasn’t consented bythe donor card scheme, their close family (or next of kin) can givepermission on their behalf for donation to occur.

The situation in the UK is an example of an ‘opt-in’ system. That isto say doctors cannot use tissues unless they have permission.However, some countries (e.g. Spain, Poland and Brazil) operate an‘opt-out’ system’ . This means that it is assumed that everyonegives consent or permission for organ donation on death, unlessthey have specifically said no or ‘opted-out’. Such countries havea much greater supply of organs.

Some groups in the UK are currently campaigning for the system tobe changed from an opt-in to an opt-out approach to increase thesupply. Critics argue that this is a very personal decision whichshouldn’t be interfered with by the State.

It should be noted that you don’t have to be dead to be an organdonor. It is possible to donate a kidney or part of your liver (a lobe)and still live healthily. These are so called “Good Samaritan” donorswho usually (although not exclusively) donate to members of theirfamily.

The ease of organ transplantation has been improved in recentyears by big leaps in the technology used to preserve the organ fortransplant outside the body. A very recent development has comeabout as a result of the work by Professor Ian Megson and his teamat the University of Edinburgh. They invented a preserving fluid,containing nitric oxide, which helps to prevent blood from clottinginside the organ. This means it can spend longer outside the bodywithout being too badly damaged before being transplanted intoits new owner. This could facilitate transporting organsinternationally for specific donors, improving the chances of a tissuematch”.

Ethical issuesSaviour siblings are children whose tissues can be used to treat abrother or sisters with a diseased organ or tissues. Pre-implantationembryo selection is used to ensure a tissue match. This practice isallowed, but very controversial

Ethics is the study of moral principles and how they relate tohuman behaviour.Just because scientists and doctors can do something, doesn’tmean to say that they should. It is up to citizens, elected politiciansand ethics committees within hospitals and universities to decideon ethical questions and debates within Biology and Medicine.The Human Tissue Act 2004 in the United Kingdom and HumanTissue (Scotland) Act 2006, is the current law which regulateswhat can be done in this area. One recent change to the law is thefact that if a person has consented to donate their organs afterdeath (for example through the donor card scheme), their relativescannot override this decision after they die.

Some of the ethical debates and questions surrounding organdonation include:• Ensuring the supply of organs for donation. The relative merits

of ‘opt-in’ and ‘opt-out’ systems. Should organs for donationsbe brought and sold? If governments won’t regulate theirsupply, then a black market tends to arise, especially fromdeveloping countries to the west.

• Genetically engineering pigs to be used for organ donationso that they match and are not rejected by humans’ immunesystems. There is also a risk of an infection jumping from onespecies to another.

• Some religious groups object to the use of animals in this wayor to the transplant of tissues from one individual to another.

Practice Questions1. (a) Why is it necessary to suppress a patient's immune system

following a transplant? (3)(b) Explain the term xenotransplant ( 2)

2. Mice have been bred so that they lack light sensitive cells in the retinaof their eyes. Scientists have then attempted to cure their blindness bytransplanting cells into the defective eyes. They have used both stemcells and cells from the retina of adult mice. Neither approach improvedvision.

(a) What is a stem cell? (2 marks)

In another study scientists transplanted precursor cells for light sensitivecells, taken from normal three- to five-day-old mice. Precursor cells arecells that have already differentiated so that they can only go on todevelop into a very limited range of cell types. After the transplant theblind mice were able to react to bright lights.

(b) Further research may show that transplanting suitable precursorcells is likely to restore human sight in some conditions. What issueswould you expect members of an Ethics Committee to consider indeciding whether to approve research on humans? (3 marks)

Answers1. (a) Because the recipients body recognises the tissue as foreign/

antigenic;Lymphocytes;Produce antibodies which attack the new tissue;Leads to rejection. (max 3)

(b) Transplantation from one species to another e.g. pig to human.

2. (a) cells that can divide indefinitely;cells are undifferentiated/not specialized;cells that can develop into any type of specialised cell

(b) source of cells;problems of xenotransplants;opt-in, opt-out argumentdangers/possible side effects;cost;

Acknowledgements:This Factsheet was researched and written by Neil RoscoeCurriculum Press, Bank House, 105 King Street, Wellington, Shropshire, TF1 1NU.Bio Factsheets may be copied free of charge by teaching staff or students, provided that their school is aregistered subscriber. No part of these Factsheets may be reproduced, stored in a retrieval system, or transmitted,in any other form or by any other means, without the prior permission of the publisher. ISSN 1351-5136